Genomic Regions Targeted by DNA Topoisomerase IIβ Frequently Interact With a Nuclear Scaffold/Matrix Protein hnRNP U/SAF‐A/SP120

Type II DNA topoisomerases (topo II) play critical roles in some cellular events through repeated cleavage/rejoining of nuclear DNA. The β isoform (topo IIβ) is essential for the transcriptional induction of neuronal genes in terminal differentiation. Genomic sites targeted by the enzyme are nonrandom. Although previous studies have claimed that topo II cleavage sites are close to the nuclear scaffold/matrix attachment region (S/MAR), it is still unclear whether this view can be generalized. We report here that a library of cloned genomic DNA fragments targeted by topo IIβ in vivo frequently contains S/MAR and binding sites for hnRNP U/SAF-A/SP120. Binding assays in vitro showed that a large proportion of the target DNAs bound to SP120 but their affinity to the nuclear scaffold/matrix varied significantly. Topo IIβ targets were extremely AT-rich and often located in gene-poor long intergenic regions (so-called gene desert) that are juxtaposed to long genes expressed in neurons under differentiation. Sequence analysis revealed that topo IIβ targets are not just AT-rich but are enriched with short tracts of A's and T's (termed A/T-patches). Their affinity to the nuclear scaffold/matrix showed a moderate positive correlation with the coverage rate of A/T-patches. The results suggest that the interaction of topo IIβ/SP120 with target regions modulates their proximity to the nuclear scaffold/matrix in a dynamic fashion and that A/T-patch is a sequence motif assisting this process.